Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni

Fanny C. Nowacki, Martin T. Swain, Oleg I. Klychnikov, Umar Niazi, Alasdair Ivens, Juan Quintana, Paul J. Hensbergen, Cornelis H. Hokke, Amy H. Buck, Karl F Hoffmann

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Penetration of skin, migration through tissues and establishment of long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies of larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role of extracellular vesicles (EVs) has yet to be considered. Here, using preparatory ultracentrifugation as well as methodologies to globally analyse both proteins and small non-coding RNAs (sncRNAs), we conducted the first characterization of Schistosoma mansoni schistosomula EVs and their potential host-regulatory cargos.

Results: Transmission electron microscopy analysis of EVs isolated from schistosomula in vitro cultures revealed the presence of numerous, 30–100 nm sized exosome-like vesicles. Proteomic analysis of these vesicles revealed a core set of 109 proteins, including homologs to those previously found enriched in other eukaryotic EVs, as well as hypothetical proteins of high abundance and currently unknown function. Characterization of E/S sncRNAs found within and outside of schistosomula EVs additionally identified the presence of potential gene-regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived small RNAs (tsRNAs; nineteen 5′ tsRNAs and fourteen 3′ tsRNAs).

Conclusions: The identification of S. mansoni EVs and the combinatorial protein/sncRNA characterization of their cargo signifies that an important new participant in the complex biology underpinning schistosome/host interactions has now been discovered. Further work defining the role of these schistosomula EVs and the function/stability of intra- and extra-vesicular sncRNA components presents tremendous opportunities for developing novel schistosomiasis diagnostics or interventions.
Original languageEnglish
Article number28665
Pages (from-to)1-16
Number of pages16
JournalJournal of Extracellular Vesicles
Volume4
Issue number1
DOIs
Publication statusPublished - 5 Oct 2015

Keywords

  • extracellular vesicles
  • small non-coding RNAs
  • miRNAs
  • tsRNAs
  • proteome
  • Schistosoma mansoni
  • platyhelminth

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